It has been shown that the most cost effective way to reduce cocaine use is by treatment. Accordingly, the National Institute on Drug Abuse has declared the development of a medication for cocaine addicts a national priority. The goal of this project is to develop substitute-agonist medications for cocaine addicts that would be similar in nature and use to methadone or the nicotine patch. This project focuses on testing a series of 15-20 cocaine analogs that are potent, selective for cocaine receptors, slow to enter the brain, and long-acting. These properties portend an effective use as a medication. In this past year, the testing has been limited to in vitro receptor binding and neurotransmitter uptake assays. These in vitro data are essential before going to in vivo studies in rodents and later in nonhuman primates. To this date, all of our findings have been positive and support the feasibility of developing a substitute agonist medication for cocaine addicts.